World Journal of Surgery

, Volume 36, Issue 11, pp 2699–2707

Prognostic MicroRNAs in Cancer Tissue from Patients Operated for Pancreatic Cancer—Five MicroRNAs in a Prognostic Index

  • Nicolai A. Schultz
  • Klaus K. Andersen
  • Anne Roslind
  • Hanni Willenbrock
  • Morten Wøjdemann
  • Julia S. Johansen
Article

DOI: 10.1007/s00268-012-1705-y

Cite this article as:
Schultz, N.A., Andersen, K.K., Roslind, A. et al. World J Surg (2012) 36: 2699. doi:10.1007/s00268-012-1705-y

Abstract

Background

The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC).

Methods

MiRNAs were purified from formalin-fixed paraffin embedded (FFPE) cancer tissue from 225 patients operated for PC. Only a few of those patients received adjuvant chemotherapy. Expressions of miRNAs were determined with the TaqMan MicroRNA Array v2.0. Two statistical methods, univariate selection and the Lasso (Least Absolute Shrinkage and Selection Operator) method, were applied in conjunction with the Cox proportional hazard model to relate miRNAs to OS.

Results

High expression of miR-212 and miR-675 and low expression of miR-148a*, miR-187, and let-7g* predicted short OS independent of age, gender, calendar year of operation, KRAS mutation status, tumor stage, American Society of Anesthesiologists (ASA) score, localization (not miR-148a*), and differentiation of tumor. A prognostic index (PI) based on these five miRNAs was calculated for each patient. The median survival was 1.09 years (Confidence Interval [CI] 0.98–1.43) for PI > median PI compared to 2.23 years (CI 1.84–4.36) for PI < median. MiR-212, miR-675, miR-187, miR-205, miR-944, miR-431, miR-194*, miR-148a*, and miR-769-5p showed the strongest prediction ability by the Lasso method. Thus miR-212, miR-675, miR-187, and miR-148a* were predictors for OS in both statistical methods.

Conclusions

The combination of five miRNAs expression in non micro-dissected FFPE PC tissue can identify patients with short OS after radical surgery. The results are independent of chemotherapy treatment. Patients with a prognostic index > median had a very short median OS of only 1 year.

Supplementary material

268_2012_1705_MOESM1_ESM.jpg (120 kb)
Supplementary Figure 1CONSORT diagram. (JPG 119kb)
268_2012_1705_MOESM2_ESM.doc (26 kb)
Supplementary Figure 2Nomogram for the multivariate survival model predicting OS in patients operated for PC. To estimate risk, calculate points for each miRNA expression in PC tissue by drawing a straight line from patients miRNA to the axis labeled “points.” Sum all points and draw a straight line from the total point axis to the 3-month, 1-year, and 10-year survival probability axes. (DOC 26 kb)

Copyright information

© Société Internationale de Chirurgie 2012

Authors and Affiliations

  • Nicolai A. Schultz
    • 1
  • Klaus K. Andersen
    • 2
  • Anne Roslind
    • 2
  • Hanni Willenbrock
    • 3
    • 4
  • Morten Wøjdemann
    • 5
  • Julia S. Johansen
    • 6
  1. 1.Department of Surgical Gastroenterology and TransplantationCopenhagen University HospitalCopenhagenDenmark
  2. 2.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  3. 3.Division of Surgery, Department of Pathology, Herlev HospitalCopenhagen University HospitalCopenhagenDenmark
  4. 4.ExiqonVedbaekDenmark
  5. 5.Division of Surgery, Department of Gastroenterology, Herlev HospitalCopenhagen University HospitalCopenhagenDenmark
  6. 6.Departments of Oncology and Medicine, Herlev HospitalCopenhagen University HospitalCopenhagenDenmark

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